Sign Out
GLUCOVANCE: Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving GLUCOVANCE, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving GLUCOVANCE, the patient should be observed closely for hypoglycemia. Metformin is negligibly bound to plasma proteins and is, therefore less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid as compared to sulfonylureas, which are extensively bound to serum proteins.
Glibenclamide: The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving GLUCOVANCE, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving GLUCOVANCE, the patient should be observed closely for loss of blood glucose control.
A possible interaction between glibenclamide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported, resulting in a potentiation of the hypoglycemic action of glibenclamide. The mechanism for this interaction is not known.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known.
Metformin hydrochloride: Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the metformin plasma and blood Cmax, by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the Cmax and AUC of furosemide were 31 % and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of metformin and furosemide when co-administered chronically.
Nifedipine: A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma metformin Cmax, and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half- life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.
Cationic drugs: In addition to the interaction with the OCT substrates/inhibitors/inducers (see DRUG INTERACTIONS), other cationic drugs (such as amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems.
Contraindicated combination: Related to glibenclamide: Miconazole (systemic route, oromucosal gel): Increase in the hypoglycaemic effect with possible onset of hypoglycaemic manifestations, or even coma (see 'Contraindication').
Combinations not recommended: Related to sulphonylurea(s): Alcohol: An antabuse syndrome (intolerance to alcohol) has occurred very rarely following the concomitant use of alcohol and glibenclamide. This effect has also been reported with chlorpropamide, glipizide and tolbutamide. Alcohol ingestion may increase the hypoglycaemic action (via inhibition of compensation reactions or delaying its metabolic inactivation), which may facilitate the onset of a hypoglycaemic coma. Avoid consumption of alcohol and alcohol-containing medications.
Phenylbutazone (systemic route): Increase in the hypoglycaemic effect of sulphonylureas (displacement of sulphonylureas from protein-binding sites and/or decrease in their elimination). Preferably use another anti-inflammatory agent exhibiting fewer interactions, or else warn the patient and step up self-monitoring; if necessary, adjust the dosage during treatment with the anti-inflammatory agent and after its withdrawal.
Related to glibenclamide: Bosentan: There is an increased risk of hepatotoxicity if bosentan is given with glibenclamide and it is recommended that such use to be avoided; the hypoglycaemic effect of glibenclamide may also be reduced.
Related to metformin: Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of fasting or malnutrition or hepatic impairment.
Iodinated contrast agents: GLUCOVANCE must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable, see DOSAGE & ADMINISTRATION and PRECAUTIONS.
Related to all antidiabetic agents: Danazol: If the combination cannot be avoided, warn the patient and step up self-monitoring of blood glucose. Possibly adjust the dosage of the antidiabetic during treatment with danazol and after its withdrawal.
Combinations to be used with caution: Related to all antidiabetic agents: Medicinal products with intrinsic hyperglycaemic activity (e.g. glucocorticoids and tetracosactides [systemic and local routes], beta-2-agonists, and chlorpromazine at high dosages of 100 mg per day, diuretics).
More frequent blood glucose monitoring may be required, especially at the beginning of treatment. If necessary, adjust the metformin dosage during therapy with the respective medicinal product and upon its discontinuation.
Angiotensin converting enzyme inhibitors (e.g. captopril, enalapril): ACE inhibitors may decrease the blood glucose levels. If necessary, adjust the dosage of GLUCOVANCE during therapy with an ACE inhibitor and upon its discontinuation.
Related to metformin: Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin, close monitoring of renal function is necessary.
Organic cation transporters (OCT): Metformin is a substrate of both transporters OCT1 and OCT2.
Co-administration of metformin with: Inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin.
Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of metformin.
Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.
Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin.
Caution is therefore advised, especially in patients with renal impairment, when these drugs are co-administered with metformin, as metformin plasma concentration may increase. If needed, and a dose adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efficacy of metformin.
Related to glibenclamide: Beta-blockers: All beta-blockers mask some of the symptoms of hypoglycaemia such as palpitations and tachycardia. Most non-cardioselective beta-blockers increase the incidence and severity of hypoglycaemia. Warn the patient and step up blood glucose self-monitoring, especially at the start of treatment.
Clonidine, reserpine, guanethidine and sympathomimetics: These substances may mask the warning symptoms of a hypoglycaemic attack. Warn the patient and step up blood glucose self-monitoring, especially at the start of treatment.
Fluconazole: Increase in the half-life of sulphonylurea with possible onset of hypoglycaemic manifestations. Warn the patient and step up self-monitoring of blood glucose, and possibly adjust the dosage of the antidiabetic during treatment with fluconazole and after its withdrawal.
Desmopressin: Reduction in antidiuretic activity.
Colesevelam: When co-administered simultaneously the plasma concentration of glibenclamide is reduced which may lead to a reduced hypoglycaemic effect. This effect was not observed when glibenclamide is given in time lag. It is recommended that GLUCOVANCE should be administered at least 4 hours prior colesevelam.
